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Evaluation of the reducing potential of PSMA-containing endosomes by FRET imaging

Cancer Drug Resistance 2021年第1期4卷 223-232页

作者： Chelvam Venkatesh jiayin shen Karson S.Putt Philip S.Low Discipline of Chemistry Indian Institute of TechnologyMadhya PradeshIndore 453552India Discipline of Bioscience and Biomedical Engineering Indian Institute of TechnologyMadhya PradeshIndore 453552India Department of Chemistry Purdue UniversityWest LafayetteIN 47907USA Institute for Drug Discovery Purdue UniversityWest LafayetteIN 47907USA

Aim:Ligand-targeted therapeutics are experiencing increasing use for treatment of human diseases due to their ability to concentrate a desired drug at a pathologic site while reducing accumulation in healthy tissues.For many ligand-targeted drug conjugates,a critical aspect of conjugate design lies in engineering release of the therapeutic payload to occur only after its internalization by targeted cells.Because disulfide bond reduction is frequently exploited to ensure intracellular drug release,an understanding of the redox properties of endocytic compartments can be critical to ligand-targeted drug design.While the redox properties of folate receptor trafficking endosomes have been previously reported,little is known about the trafficking of prostate-specific membrane antigen(PSMA),a receptor that is experiencing increasing use for drug targeting in humans.Methods:To obtain this information,we have constructed a PSMA-targeted fluorescence resonance energy transfer pair that reports on disulfide bond reduction by changing fluorescence from red to green.Results:We show here that this reporter exhibits rapid and selective uptake by PSMA-positive cells,and that reduction of its disulfide bond proceeds steadily but incompletely following internalization.The fact that maximal disulfide reduction reaches only~50%,even after 24 h incubation,suggests that roughly half of the conjugates must traffic through endosomes that display no reducing capacity.Conclusion:As the level of disulfide reduction differs between PSMA trafficked and previously published folate trafficked conjugates,it also follows that not all internalizing receptors are translocated through similar intracellular compartments.Taken together,these data suggest that the efficiency of disulfide bond reduction must be independently analyzed for each receptor trafficking pathway when disulfide bond reduction is exploited for intracellular drug release.

关键词： DUPA prostate-specific membrane antigen endosomes endocytosis

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Common genetic heterogeneity of human interleukin-37 leads to functional variance

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Cellular & Molecular Immunology 2017年第9期14卷 783-791页

作者： Jingjing Yan Yuling Zhang Shimeng Cheng Bin Kang Jinbiao Peng Xiaodan Zhang Meichun Yuan Wenqi Chu Wen Zhang jiayin shen Shuye Zhang Shanghai Public Health Clinical Center and Institutes of Biomedical Sciences Fudan UniversityShanghaiChina School of Life Sciences Hebei Normal UniversityShi-JiazhuangHebei Key Laboratory of Medical Molecular Virology of Ministries of Education/Health Institute of Medical MicrobiologyShanghai Medical College of Fudan UniversityShanghaiChina

Interleukin-37(IL-37)is an inhibitory member of the IL-1 family of cytokines.We previously found that balanced selection maintains common variations of the human IL37 gene.However,the functional consequences of this selection have yet to be validated.Here,using cells expressing exogenous IL-37 variants,including IL-37 Ref and IL-37 Var1 and Var2,we found that the three variants of IL-37 exhibited different immunoregulatory potencies in response to immune stimulation.The protein level of IL-37 Var2 was found to be significantly less than that of IL-37 Ref or Var1,despite the comparable mRNA levels of all three variants.Further study showed that IL-37 Var2 was rapidly degraded by a proteasome-dependent mechanism mediated by enhanced polyubiquitination,leading to a transient upregulation of IL-37 Var2 after immune stimulation.Finally,when ectopically expressed in cells,human IL-37 Var2 exerted less inhibition on proinflammatory cytokine production than did other IL-37 variants.Conversely,purified extracellular IL-37 variant proteins demonstrated comparable inhibitory abilities in vitro.In conclusion,our study reveals that common genetic variants of IL37 lead to different immune-inhibitory potencies,primarily as a result of differences in IL-37 protein stability,suggesting the possible involvement of these variants in various human diseases.

关键词： Cytokine gene variation inflammation protein stability

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Evaluation of Epstein-Barr Virus Salivary Shedding in HIV/AIDS Patients and HAART Use: A Retrospective Cohort Study

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Virologica Sinica 2018年第3期33卷 227-233页

作者： Yan Yan Yong Ren Renfang Chen Jing Hu Yongjia Ji Junyang Yang jiayin shen Lvyin Hu Hao Pei Jun Wang Yuanwang Qiu Hongzhou Lu Lihua Huang Center of Clinical Laboratory The Fifth People’s Hospital of Wuxi Affiliated to Jiangnan University Wuxi Institute of Hepatology The Fifth People’s Hospital of Wuxi Affiliated to Jiangnan University The International Joint Research Laboratory for Infection and Immunity (China-Germany) The Fifth People’s Hospital of Wuxi Affiliated to Jiangnan University Wuxi Red Ribbon Care Center of China Red Cross The Fifth People’s Hospital of Wuxi Affiliated to Jiangnan University The International Joint Research Laboratory for Infection and Immunity (China-Germany) Wuxi School of MedicineJiangnan University Department of Infectious Diseases Shanghai Public Health Clinical Center Fudan University

Little data is available on the evaluation of the occurrence rates of Epstein-Barr virus(EBV) in saliva and relationship with highly active antiretroviral therapy(HAART) use in HIV/AIDS patients in China. We conducted a retrospective cohort study of EBV serological tests for HIV/AIDS patients who were treated in the hospitals for infectious diseases in Wuxi and Shanghai, China from May 2016 to April 2017. The EBV-seropositive samples were identified by ELISA. EBV-specific primers and probes were used for the quantitative detection of viral DNA from saliva via quantitative real-time polymerase chain reaction. CD4 cell counts of the HIV/AIDS patients were detected by a flow cytometry. A total of 372 HIV/AIDS patients were ultimately selected and categorized for this retrospective cohort study. For EBV IgG and IgM, the HIV/AIDS HAART use(H) and non-HAART use(NH) groups had significantly higher seropositive rates than the HIV-negative control group. The HIV/AIDS(NH) group had the highest seropositive rate(IgG, 94.27%; IgM, 68.98%) and the highest incidence of EBV reactivation or infection. For salivary EBV DNA-positive rates and quantities, the HIV/AIDS(H)(73.69%) and the HIV/AIDS(NH)(100%) groups showed significantly higher values than the HIV-negative control group(35.79%,[ twofold). Further, the salivary EBV DNA-negative population had significantly higher CD4 cell counts than the EBV DNA-positive population in the HIV/AIDS(H) group and the HIV/AIDS(NH) groups. Thus, HAART use is beneficial in decreasing the EBV salivary shedding in HIV/AIDS patients and indirectly decreases EBV transmission risk.

关键词：唾液病毒评估聚合酶链反应 EBV ELISA DNA 传染疾病

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面向车辆边缘计算的多目标任务卸载算法

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铁路计算机应用 2024年第3期33卷 13-18页

作者：王忠峰王小进高鹏申佳胤徐佳国铁吉讯科技有限公司北京100081 南京邮电大学江苏省大数据安全与智能处理重点实验室南京210023 中国铁道科学研究院集团有限公司电子计算技术研究所北京100081

为解决车联网动态环境下,计算和通信资源不足时的任务卸载问题,提出一种基于车辆边缘计算的多目标任务卸载算法。搭建车辆边缘计算中的通信模型和计算模型,考虑每个车辆应用的任务时延约束,设计了多目标优化目标函数,联合优化时延和能... 详细信息

为解决车联网动态环境下,计算和通信资源不足时的任务卸载问题,提出一种基于车辆边缘计算的多目标任务卸载算法。搭建车辆边缘计算中的通信模型和计算模型,考虑每个车辆应用的任务时延约束,设计了多目标优化目标函数,联合优化时延和能耗成本;引入交叉变异、非支配排序、拥挤度排序等技术,提出了多目标任务卸载算法。实验表明,相比于其他任务卸载算法,所提算法显著减少了处理任务的时间和能耗。

关键词：车联网车辆边缘计算任务卸载调度遗传算法多目标优化

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Rolling Decision Model of Thermal Power Retrofit and Generation Expansion Planning Considering Carbon Emissions and Power Balance Risk

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Energy Engineering 2024年第5期121卷 1309-1328页

作者： Dong Pan Xu Gui jiayin Xu Yuming shen Haoran Xu Yinghao Ma Economic and Technology Research Institute State Grid Anhui Electric Power Co.Ltd.Hefei230022China School of Electrical and Automation Engineering Hefei University of TechnologyHefei230009China

With the increasing urgency of the carbon emission reduction task,the generation expansion planning process needs to add carbon emission risk constraints,in addition to considering the level of power adequacy.However,methods for quantifying and assessing carbon emissions and operational risks are lacking.It results in excessive carbon emissions and frequent load-shedding on some days,although meeting annual carbon emission reduction targets.First,in response to the above problems,carbon emission and power balance risk assessment indicators and assessment methods,were proposed to quantify electricity abundance and carbon emission risk level of power planning scenarios,considering power supply regulation and renewable energy fluctuation characteristics.Secondly,building on traditional two-tier models for low-carbon power planning,including investment decisions and operational simulations,considering carbon emissions and power balance risks in lower-tier operational simulations,a two-tier rolling model for thermal power retrofit and generation expansion planning was established.The model includes an investment tier and operation assessment tier and makes year-by-year decisions on the number of thermal power units to be retrofitted and the type and capacity of units to be commissioned.Finally,the rationality and validity of the model were verified through an example analysis,a small-scale power supply system in a certain region is taken as an example.The model can significantly reduce the number of days of carbon emissions risk and ensure that the power balance risk is within the safe limit.

关键词： Carbon emission risk power balance risk thermal power retrofit generation expansion planning

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Cell Wall Fixation,Translocation,and Vacuolar Detoxification of Cadmium Contribute to Differential Grain Cadmium Accumulation in Two Rice Cultivars

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Rice science 2024年第3期31卷 241-244,I0008-I0010页

作者： ZHU Xiaofang ZHAO Ling HUANG Jing HE Jiatong SONG jiayin TENG Ying shen Renfang State Key Laboratory of Soil and Sustainable Agriculture Institute of Soil ScienceChinese Academy of ScienceNanjing 210008China State Key Laboratory of Subtropical Silviculture Zhejiang A&F UniversityHangzhou 311300China

Cadmium(Cd)toxicity in rice is a major concern for human health and the environment,as it can accumulate in rice grains when grown in Cd-contaminated soils.To mitigate the risk of Cd toxicity,it is crucial to cultivate rice varieties with low grain Cd accumulation.In the summers of 2021 and 2022,we conducted Cd analysis on two rice cultivars,Tianyouhuazhan(TYHZ)and Xiushui 14,grown in fields with varying Cd pollution levels.These cultivars were also subjected to hydroponic treatment with or without 1μmol/L Cd for 7 d to assess Cd accumulation,nitric oxide(NO)production。

关键词： cultivar soils pollution

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Viromes of Haemaphysalis longicornis reveal different viral abundance and diversity in free and engorged ticks

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Virologica Sinica 2024年第2期39卷 194-204页

作者： Jian Xiao Xuan Yao Xuhua Guan Jinfeng Xiong Yaohui Fang Jingyuan Zhang You Zhang Abulimiti Moming Zhengyuan Su jiayin Jin Yingying Ge Jun Wang Zhaojun Fan Shuang Tang Shu shen Fei Deng Key Laboratory of Virology and Biosafety and National Virus Resource Center Wuhan Institute of VirologyChinese Academy of SciencesWuhan430071China Hubei Provincial Center for Disease Control and Prevention Wuhan430070China University of Chinese Academy of Sciences Beijing101408China Hubei Jiangxia Laboratory Wuhan430200China Xinjiang Key Laboratory of Vector-borne Infectious Diseases Urumqi830002China Current address:Department of Medical Laboratory The Second Affiliated HospitalHainan Medical UniversityHaikou57000China

Haemaphysalis longicornis ticks,commonly found in East Asia,can transmit various pathogenic viruses,includingthe severe fever with thrombocytopenia syndrome virus(SFTSV)that has caused febrile diseases among humansin Hubei Province.However,understanding of the viromes of H.longicornis was limited,and the prevalence ofviruses among H.longicornis ticks in Hubei was not well clarified.This study investigates the viromes of bothengorged(fed)and free(unfed)H.longicornis ticks across three mountainous regions in Hubei Province from 2019to 2020.RNA-sequencing analysis identified viral sequences that were related to 39 reference viruses belonging tounclassified viruses and seven RNA viral families,namely Chuviridae,Nairoviridae,Orthomyxoviridae,Parvoviridae,Phenuiviridae,Rhabdoviridae,and Totiviridae.Viral abundance and diversity in these ticks were analysed,andphylogenetic characteristics of the Henan tick virus(HNTV),Dabieshan tick virus(DBSTV),Okutama tick virus(OKTV),and Jingmen tick virus(JMTV)were elucidated based on their full genomic sequences.Prevalenceanalysis demonstrated that DBSTV was the most common virus found in individual H.longicornis ticks(12.59%),followed by HNTV(0.35%),whereas JMTV and OKTV were not detected.These results improve our understanding of H.longicornis tick viromes in central China and highlight the role of tick feeding status and geographyin shaping the viral community.The findings of new viral strains and their potential impact on public health raisethe need to strengthen surveillance efforts for comprehensively assessing their spillover potentials.

关键词： Ticks Virome Haemaphysalis longicornis Phylogenetic analysis Viral abundance and diversity

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Uplifting of AdS type to quintessence-like potential induced by frozen large-scale Lorentz violation

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Chinese Physics C 2020年第8期44卷 180-192页

作者：翟韩豫申佳音薛迅 Department of Physics East China Normal UniversityShanghai 200241China Center for Theoretical Physics Xinjiang UniversityUrumqi 830046China

The quintessence-like potential of vacuum energy can meet the requirements from both quantum gravity and the accelerating expansion of the universe.The anti-de Sitter(AdS)vacuum in string theory must be lifted to the meta-stable dS vacuum with a positive vacuum energy density to explain the accelerating expansion of the universe.Based on possible large-scale Lorentz violation,we define an effective cosmological constant that depends not only on the bare cosmological constant but also on the Lorentz violation effect.We find that the evolution of the effective cosmological constant exhibits the behavior of the quintessence potential when the bare cosmological constant originates from the string landscape,in contrast to the existence of a local minimum during evolution when the bare cosmological constant is supplied by the swampland.The critical value of the bare cosmological constant is approximately zero for the behavior transition.The frozen large-scale Lorentz violation can uplift the AdS vacua to an effective quintessence-like one in this sense.

关键词： Lorentz violation dark energy inflation quintessence landscape

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Comprehensive Strategic Planning and Enhancement of China CDC Contributes to High-Quality Development of the National Disease Control and Prevention System

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China CDC weekly 2024年第4期6卷 61-63页

作者： Hongbing shen Director-General of China CDC Academician of the Chinese Academy of EngineeringBeijingChina

The Chinese government has always attached great importance to disease control and prevention efforts.Recently,the general office of China’s State Council issued the“Guidelines for High-Quality Development of Disease Prevention and Control”(hereinafter referred to as the“Guidelines”)(1).The Guidelines focus on promoting high-quality development of disease control and prevention and the strategic goal of“Healthy China,”providing specific implementation pathways for the development of national disease control and prevention in the new era,including overall planning,restructuring of governance,enhancing core capabilities,strengthening talent development,and improving organizational support.

关键词： prevention attached Quality

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A Systematic Analysis of Early Life Exposure to the Chinese Famine(1959-1961)and the Health of Older Adults-China,2008-2023

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China CDC weekly 2024年第11期6卷 203-207,I0001-I0003页

作者： Chi shen Xi Chen School of Public Policy and Administration Xi’an Jiaotong UniversityXi’an CityShaanxi ProvinceChina Department of Health Policy and Management Yale School of Public HealthNew HavenCTU.S Department of Economics Yale UniversityNew HavenCTU.S

What is already known about this topic?There is mounting evidence indicating that the aging process initiates during early life stages,with in utero the individual’s environment playing a significant role.Consequently,it is crucial to comprehend the enduring effects of early life circumstances on health in old age.What is added by this report?In this study,we conducted a meta-analysis to examine the effects of the Chinese Famine(1959–1961)on the health of older adults.We also explored potential mechanisms underlying these effects.What are the implications for public health practice?The complex interplay between early life circumstances,multiple health-related sectors,and healthy aging necessitates a comprehensive life-course approach and strategic interventions to enhance public health in an aging society.

关键词： life aging mount

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